A member of the Corneliagens, Scipio served as consul in 218 BC, the first year of the Second Punic War.[1] He sailed with his army from Pisa with the intention of confronting Hannibal in Hispania.[2] Stopping at Massalia (today Marseille) to replenish his supplies, he was shocked to discover that Hannibal's army had moved from Hispania and was crossing the Rhône.[2] Scipio disembarked his army and marched to confront Hannibal, who, by now, had moved on. Returning to the fleet, he entrusted the command of his army to his brother Gnaeus Cornelius Scipio Calvus and sent him off to Hispania to carry on with the originally intended mission. Scipio returned to Italy to take command of the troops fighting in Cisalpine Gaul.[3]

On his return to Italy, he advanced at once to meet Hannibal. In a sharp cavalry engagement near the Ticinus, a tributary of the Po river, he was defeated and severely wounded.[1] In December of the same year, he again witnessed the complete defeat of the Roman army at the Trebia, when his fellow consul Tiberius Sempronius Longus allegedly insisted on fighting against his advice.[1] [The earliest historical source was by the Greek historian Polybius, who became an intimate of Scipio's grandson and was seemingly biased in favour of the Scipio family. The other major account was written in the following century by the Roman historian Livy, who also expressed bias in favour of certain aristocratic families.][4]

Despite the military defeats, he still retained the confidence of the Roman people; his term of command was extended and the following year found him in Hispania with his brother Calvus, winning victories over the Carthaginians and strengthening Rome's position in the Iberian peninsula. He continued the Iberian campaigns until 211, when he was killed during the defeat of his army at the upper Baetis river by the Carthaginians and their Iberian allies under Indibilis and Mandonius. That same year, Calvus and his army were destroyed at Ilorci near Carthago Nova. The details of these campaigns are not completely known, but it seems that the ultimate defeat and death of the two Scipiones was due to the desertion of the Celtiberians, who were bribed by Hasdrubal Barca, Hannibal's brother.[1]

A later Publius Cornelius Scipio, son of Scipio Africanus the elder and Aemilia Paulla, and grandson of the consul of 218 BC, was the adoptive father of Scipio Aemilianus Africanus. This latter Scipio served as praetor in 174 BC.